Phase I trial of CJRB-101 plus pembrolizumab in patients with metastatic non-small cell lung cancer, head and neck squamous cell carcinoma and melanoma
Published report from the trial registered as NCT05877430, in Journal for ImmunoTherapy of Cancer (2026), chosen as the most cited paper whose own text cites the registry id.
Overview
Background: Dysbiosis of gut microbiome leads to resistance to immunotherapy in various advanced solid tumors. CJRB-101 is a live biotherapeutic product consisting of a novel strain belonging to the species Leuconostoc mesenteroides. To modulate the tumor microenvironment, CJRB-101 was combined with pembrolizumab.
Methods: Preclinical efficacy and mechanistic studies were performed using humanized non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) models. This is a multicenter, first-in-human, two-part, phase I, open-label study of CJRB-101 (1×10 11 or 4×10 11 colony forming unit (CFU)/day) plus pembrolizumab (200 mg every three weeks (Q3W)) in advanced NSCLC, melanoma, and head and neck squamous cell carcinoma in both immune checkpoint inhibitor (ICI)-naive and ICI-refractory settings. The primary endpoint was to assess the dose-limiting toxicities (DLTs), adverse events, and preliminary activity of the combination treatment. Exploratory endpoints included stool metagenomics analysis and pharmacodynamics parameters.
Results: In four PDX models, CJRB-101 with pembrolizumab demonstrated enhanced antitumor efficacy, showing a tumor growth inhibition (TGI) of 77.3% in the CJRB-101 monotherapy group and 61.9% in the combination group, which was significantly improved compared with pembrolizumab alone. A distinct M2-to-M1 repolarization was observed and validated in vitro. Notably, increased activation of cytotoxic T cells was observed, suggesting an immune-mediated antitumor mechanism of CJRB-101. A total of 42 patients were enrolled in the low-dose cohort (one capsule once a day; n=6) and high-dose cohort (two capsules two times a day, n=36). Metastatic NSCLC accounted for 86% (n=36) and 67% (n=28) of the patients were refractory to ICIs. None of the patients experienced DLT. In ICI-naïve NSCLC (n=12) with programmed death-ligand 1 (PD-L1) >50%, the overall response rate (ORR) and disease control rate (DCR) were 58% and 75%, respectively. The ORR was 5% and DCR was 41% in the ICI-refractory NSCLC (n=22) with an ORR of 5% and DCR of 41%. After a median follow-up of 15.6 months and 8.9 months for ICI-naïve and ICI-refractory NSCLC, the median progression-free survival was 9 months (95% CI 5.6 to not reached) and 1.8 months (95% CI 1.6 to 4.3), respectively. CJRB-101 plus pembrolizumab was well-tolerated, and none of the patients experienced grade > 3 treatment-related adverse events.
Conclusions: Early clinical data show encouraging antitumor response of CJRB-101 plus pembrolizumab in ICI-naïve metastatic NSCLC with PD-L1 > 50%.
Trial registration number: NCT05877430.
Indexed on Europe PMC as PubMed record 42140743 (DOI 10.1136/jitc-2025-014702). Its abstract cites the registry id NCT05877430, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT05877430 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.